General anaesthesia in sickle-cell disease.
General anaesthesia was administered on 284 occasions to 200 patients with sickle-cell disease at one hospital during July 1958 to June 1978. No intraoperative but six postoperative deaths occurred. The management of anaesthesia may have contributed to two of the postoperative deaths. Clinically uneventful anaesthesia did not appear to provoke severe sickling crises or to be responsible for mortality, but a contribution to postoperative morbidity could not be excluded. A simple, careful anaesthetic technique and selective but not routine blood transfusion appears to be associated with minimal anaesthetic morbidity and mortality in patients with sickle-cell disease.


Sperm morphology and sperm velocity in passerine birds.
Sperm velocity is one of the main determinants of the outcome of sperm competition. Since sperm vary considerably in their morphology between and within species, it seems likely that sperm morphology is associated with sperm velocity. Theory predicts that sperm velocity may be increased by enlarged midpiece (energetic component) or flagellum length (kinetic component), or by particular ratios between sperm components, such as between flagellum length and head size. However, such associations have rarely been found in empirical studies. In a comparative framework in passerine birds, we tested these theoretical predictions both across a wide range of species and within a single family, the New World blackbirds (Icteridae). In both study groups, sperm velocity was influenced by sperm morphology in the predicted direction. Consistent with theoretical models, these results show that selection on sperm morphology and velocity are likely to be concomitant evolutionary forces.


Development and Validation of 58K SNP-Array and High-Density Linkage Map in Nile Tilapia (O. niloticus).
Despite being the second most important aquaculture species in the world accounting for 7.4% of global production in 2015, tilapia aquaculture has lacked genomic tools like SNP-arrays and high-density linkage maps to improve selection accuracy and accelerate genetic progress. In this paper, we describe the development of a genotyping array containing more than 58,000 SNPs for Nile tilapia (Oreochromis niloticus). SNPs were identified from whole genome resequencing of 32 individuals from the commercial population of the Genomar strain, and were selected for the SNP-array based on polymorphic information content and physical distribution across the genome using the Orenil1.1 genome assembly as reference sequence. SNP-performance was evaluated by genotyping 4991 individuals, including 689 offspring belonging to 41 full-sib families, which revealed high-quality genotype data for 43,588 SNPs. A preliminary genetic linkage map was constructed using Lepmap2 which in turn was integrated with information from the O_niloticus_UMD1 genome assembly to produce an integrated physical and genetic linkage map comprising 40,186 SNPs distributed across 22 linkage groups (LGs). Around one-third of the LGs showed a different recombination rate between sexes, with the female being greater than the male map by a factor of 1.2 (1632.9 to 1359.6 cM, respectively), with most LGs displaying a sigmoid recombination profile. Finally, the sex-determining locus was mapped to position 40.53 cM on LG23, in the vicinity of the anti-Müllerian hormone (amh) gene. These new resources has the potential to greatly influence and improve the genetic gain when applying genomic selection and surpass the difficulties of efficient selection for invasively measured traits in Nile tilapia.


Mantle wedge diapirs detected by a dense seismic array in Northern Taiwan.
It is conventionally believed that magma generation beneath the volcanic arc is triggered by the infiltration of fluids or melts derived from the subducted slab. However, recently geochemical analyses argue the arc magma may be formed by mélange diapirs that are physically mixed by sediment, altered oceanic crust, fluids, and mantle above the subducted slab. Further numerical modeling predicts that the mantle wedge diapirs have significant seismic velocity anomalies, even though these have not been observed yet. Here we show that unambiguously later P-waves scattered from some obstacles in the mantle wedge are well recorded at a dense seismic array (Formosa Array) in northern Taiwan. It is the first detection of seismic scattering obstacles in the mantle wedge. Although the exact shape and size of the scattered obstacles are not well constrained by the arrival-times of the later P-waves, the first order approximation of several spheres with radius of ~ 1 km provides a plausible interpretation. Since these obstacles were located just beneath the magma reservoirs around depths between 60 and 95 km, we conclude they may be mantle wedge diapirs that are likely associated with magma generation beneath active volcanoes.


Enasidenib: An Oral IDH2 Inhibitor for the Treatment of Acute Myeloid Leukemia.
Acute myeloid leukemia (AML) is a hematologic malignancy that affects predominantly older patients, with a median age of diagnosis around 67. Overall prognosis is poor; however, novel targeted therapies that can potentially improve outcomes in these patients have emerged in recent years. Mutations in isocitrate dehydrogenase (IDH) occur in 20% of AML diagnoses. IDH2 performs a crucial role in cellular metabolism, and when this enzyme is inhibited, the cell cannot rid itself of endogenous products and is thus marked for apoptosis. The US Food and Drug Administration (FDA) approved the first mutant IDH2 inhibitor, enasidenib, for patients with relapsed or refractory IDH2-mutated AML detected by an FDA-approved test.


Evidence-based psychotherapy for schizophrenia: 2011 update.
Many patients with schizophrenia have psychological distress and receive some form of psychotherapy. Several different psychotherapeutic approaches for schizophrenia have been developed and studied. Of these approaches, cognitive behavior therapy (CBT) has the strongest evidence base and has shown benefit for symptom reduction in outpatients with residual symptoms. In addition to CBT, other approaches include compliance therapy, personal therapy, acceptance and commitment therapy, and supportive therapy. Although usually studied as distinct approaches, these therapies overlap with each other in their therapeutic elements. Psychotherapy for schizophrenia continues to evolve with the recent advent of such approaches as metacognitive therapy, narrative therapies, and mindfulness therapy. Future research may also consider three different goals of psychotherapy in this patient population: to provide emotional support, to enhance functional recovery, and to alter the underlying illness process.


Insights into plant cell wall degradation from the genome sequence of the soil bacterium Cellvibrio japonicus.
The plant cell wall, which consists of a highly complex array of interconnecting polysaccharides, is the most abundant source of organic carbon in the biosphere. Microorganisms that degrade the plant cell wall synthesize an extensive portfolio of hydrolytic enzymes that display highly complex molecular architectures. To unravel the intricate repertoire of plant cell wall-degrading enzymes synthesized by the saprophytic soil bacterium Cellvibrio japonicus, we sequenced and analyzed its genome, which predicts that the bacterium contains the complete repertoire of enzymes required to degrade plant cell wall and storage polysaccharides. Approximately one-third of these putative proteins (57) are predicted to contain carbohydrate binding modules derived from 13 of the 49 known families. Sequence analysis reveals approximately 130 predicted glycoside hydrolases that target the major structural and storage plant polysaccharides. In common with that of the colonic prokaryote Bacteroides thetaiotaomicron, the genome of C. japonicus is predicted to encode a large number of GH43 enzymes, suggesting that the extensive arabinose decorations appended to pectins and xylans may represent a major nutrient source, not just for intestinal bacteria but also for microorganisms that occupy terrestrial ecosystems. The results presented here predict that C. japonicus possesses an extensive range of glycoside hydrolases, lyases, and esterases. Most importantly, the genome of C. japonicus is remarkably similar to that of the gram-negative marine bacterium, Saccharophagus degradans 2-40(T). Approximately 50% of the predicted C. japonicus plant-degradative apparatus appears to be shared with S. degradans, consistent with the utilization of plant-derived complex carbohydrates as a major substrate by both organisms.


Cesarean delivery for twins: a systematic review and meta-analysis.
We undertook a systematic review and meta-analysis to determine whether a policy of planned cesarean section or vaginal delivery is better for twins. We searched MEDLINE and EMBASE from 1980 through May 2001 using combinations of the following terms: twin, delivery, cesarean section, vaginal birth, birth weight, and gestational age. Studies that compared planned cesarean section to planned vaginal birth for babies weighing at least 1500 g or reaching at least 32 weeks' gestation were included. We computed pooled odds ratios for perinatal or neonatal mortality, low 5-minute Apgar score, neonatal morbidity, and maternal morbidity. The infant was the unit of statistical analysis. Results were considered statistically significant if the 95% CI did not encompass 1.0. We retrieved 67 articles, 63 of which were excluded. Four studies with a total of 1932 infants were included in the analysis. A low 5-minute Apgar score occurred less frequently in twins delivered by planned cesarean section (odds ratio, 0.47; 95% CI, 0.26-0.88) principally because of a reduction among twins if twin A was in breech position (odds ratio, 0.33; 95% CI, 0.17-0.65). Twins delivered by planned cesarean section spent significantly longer in the hospital (mean difference, 4.01 days; 95% CI, 0.73-7.28 days). There were no significant differences in perinatal or neonatal mortality, neonatal morbidity, or maternal morbidity. Planned cesarean section may decrease the risk of a low 5-minute Apgar score, particularly if twin A is breech. Otherwise, there is no evidence to support planned cesarean section for twins.


Relationship between contents of leucoanthocyanidin and dhurrin in sorghum leaves.
Flag leaves of 'Colman' forage sorghum (Sorghum bicolor) contain at least 25 times as much leucoanthocyanidin (LAC) and approximately half as much of the cyanogenic glucoside, dhurrin, as do flag leaves of 'White Collier' forage sorghum. Assays of flag leaves from 119 F2 plants and 11 F5 lines from crosses between these two cultivars revealed a statistically significant negative association between levels of LAC and dhurrin. Both LAC and dhurrin are aromatic compounds, and the negative association between the two may be the result of competition for intermediates or products of the aromatic biosynthetic pathway. This rationale appears to be quite different from that for the negative association reported for levels of tannin and cyanide in Lotus corniculatus. Although the negative relationship between LAC and dhurrin in sorghum was statistically significant, the association was not consistent enough to suggest that either trait could be used reliably in selecting or breeding to modify the other trait.


Blood Metabolomic Measures Associate With Present and Future Glycemic Control in Type 2 Diabetes.
We studied whether blood metabolomic measures in people with type 2 diabetes (T2D) are associated with insufficient glycemic control and whether this association is influenced differentially by various diabetes drugs. We then tested whether the same metabolomic profiles were associated with the initiation of insulin therapy. A total of 162 metabolomic measures were analyzed using a nuclear magnetic resonance-based method in people with T2D from four cohort studies (n = 2641) and one replication cohort (n = 395). Linear and logistic regression analyses with adjustment for potential confounders, followed by meta-analyses, were performed to analyze associations with hemoglobin A1c levels, six glucose-lowering drug categories, and insulin initiation during a 7-year follow-up period (n = 698). After Bonferroni correction, 26 measures were associated with insufficient glycemic control (HbA1c >53 mmol/mol). The strongest association was with glutamine (OR, 0.66; 95% CI, 0.61 to 0.73; P = 7.6 × 10-19). In addition, compared with treatment-naive patients, 31 metabolomic measures were associated with glucose-lowering drug use (representing various metabolite categories; P ≤ 3.1 × 10-4 for all). In drug-stratified analyses, associations with insufficient glycemic control were only mildly affected by different glucose-lowering drugs. Five of the 26 metabolomic measures (apolipoprotein A1 and medium high-density lipoprotein subclasses) were also associated with insulin initiation during follow-up in both discovery and replication. The strongest association was observed for medium high-density lipoprotein cholesteryl ester (OR, 0.54; 95% CI, 0.42 to 0.71; P = 4.5 × 10-6). Blood metabolomic measures were associated with present and future glycemic control and might thus provide relevant cues to identify those at increased risk of treatment failure.


Understanding public trust in services provided by community pharmacists relative to those provided by general practitioners: a qualitative study.
To apply sociological theories to understand public trust in extended services provided by community pharmacists relative to those provided by general practitioners (GPs). Qualitative study involving focus groups with members of the public. The West of Scotland. 26 purposively sampled members of the public were involved in one of five focus groups. The groups were composed to represent known groups of users and non-users of community pharmacy, namely mothers with young children, seniors and men. Trust was seen as being crucial in healthcare settings. Focus group discussions revealed that participants were inclined to draw unfavourable comparisons between pharmacists and GPs. Importantly, participants' trust in GPs was greater than that in pharmacists. Participants considered pharmacists to be primarily involved in medicine supply, and awareness of the pharmacist's extended role was low. Participants were often reluctant to trust pharmacists to deliver unfamiliar services, particularly those perceived to be 'high risk'. Numerous system-based factors were identified, which reinforce patient trust and confidence in GPs, including GP registration and appointment systems, GPs' expert/gatekeeper role and practice environments. Our data indicate that the nature and context of public interactions with GPs fostered familiarity with a specific GP or practice, which allowed interpersonal trust to develop. By contrast, participants' exposure to community pharmacists was limited. Additionally, a good understanding of the GPs' level of training and role promoted confidence. Current UK initiatives, which aim to implement a range of pharmacist-led services, are undermined by lack of public trust. It seems improbable that the public will trust pharmacists to deliver unfamiliar services, which are perceived to be 'high risk', unless health systems change in a way that promotes trust in pharmacists. This may be achieved by increasing the quality and quantity of patient interactions with pharmacists and gaining GP support for extended pharmacy services.


Quantitative autoradiographic assessment of 55Fe-RBC distribution in rat brain.
A simple in vivo technique of labeling erythrocytes (RBCs) with 55Fe was developed for quantitative autoradiography (QAR). This procedure involved injecting 5-6 ml of [55Fe]ferrous citrate solution (1 mCi/ml) intraperitoneally into donor rats. The number of labeled RBCs reached a maximum at around 7 days and declined very slowly thereafter. Labeled RBCs were harvested from donor rats and used for RBC volume measurement in awake rats. Brain radioactivity was assayed by QAR, which yielded spatial resolution of greater than 50 microns. Tight nearly irreversible binding of 55Fe to RBCs was found in vivo and in vitro. More than 99.5% of the 55Fe in the blood of donor rats was bound to RBCs. Because of this, labeled blood can be taken from donors and injected into recipients without further preparation. The tissue absorption of 55Fe emissions was the same in gray and white matter. Microvascular RBC volumes measured with 55Fe-labeled RBCs agreed with those assayed with 51Cr-labeled RBCs for many, but not all, brain areas. In conclusion, 55Fe-RBCs can be readily prepared by this technique and accurately quantitated in brain tissue by QAR.


Search for a neutral Higgs boson decaying to a W boson pair in pp collisions at square root of s = 1.96 TeV.
We present the results of a search for standard model Higgs boson production with decay to WW*, identified through the leptonic final states e+ e- nu nu,+/-mu -/+nu nu and mu+ mu- nu nu. This search uses 360 pb -1 of data collected from pp collisions at square root of s =1.96 TeV by the upgraded Collider Detector at Fermilab (CDF II). We observe no signal excess and set 95% confidence level upper limits on the production cross section times branching ratio for the Higgs boson to WW* or any new scalar particle with similar decay products. These upper limits range from 5.5 to 3.2 pb for Higgs boson masses between 120 and 200 GeV/c2.


Involvement of serotonin in the excitation of phrenic motoneurons evoked by stimulation of the raphe obscurus.
Short-latency averaged responses in the C5 phrenic nerves to electrical stimulation (2.5-80 microA; 5-80 Hz; 150 microseconds pulse duration) of raphe pallidus (RP) and raphe obscurus (RO) were investigated in anesthetized, paralyzed, and artificially ventilated cats. The responses to stimulation of RO were excitatory, whereas a mixture of inhibitory and excitatory responses of lesser magnitude were observed after stimulating in RP. The maximal response was obtained from the ventral part of RO and consisted of early and delayed excitatory responses that were of equal magnitude in both left and right C5 phrenic nerve roots. The mean latency for the early response was 2.5 +/- 0.1 msec and for the delayed response was 7.0 +/- 0.2 msec. Both responses were elicited during inspiratory phase stimulation, but only the delayed response was present during expiratory phase stimulation. The stimulus threshold of the early response was 5 microA; the delayed response was elicited at currents as small as 2.5 microA. Early and delayed responses were affected in different ways by increasing stimulus current and by increasing stimulus frequency. Intravenous administration of serotonin receptor antagonists methysergide (0.1-0.7 mg/kg), metergoline (33-244 micrograms/kg), and cinanserin (1.5-9.0 micrograms/kg) caused significant dose-related reductions in the magnitude of the delayed response, but did not significantly affect the early response. These data suggest that the early and delayed excitatory responses are mediated by different neuronal pathways. The early response does not involve serotonin release, while the later response is mediated at least in part by activation of a serotonergic pathway.(ABSTRACT TRUNCATED AT 250 WORDS)


Provision of spiritual care to patients with advanced cancer: associations with medical care and quality of life near death.
To determine whether spiritual care from the medical team impacts medical care received and quality of life (QoL) at the end of life (EoL) and to examine these relationships according to patient religious coping. Prospective, multisite study of patients with advanced cancer from September 2002 through August 2008. We interviewed 343 patients at baseline and observed them (median, 116 days) until death. Spiritual care was defined by patient-rated support of spiritual needs by the medical team and receipt of pastoral care services. The Brief Religious Coping Scale (RCOPE) assessed positive religious coping. EoL outcomes included patient QoL and receipt of hospice and any aggressive care (eg, resuscitation). Analyses were adjusted for potential confounders and repeated according to median-split religious coping. Patients whose spiritual needs were largely or completely supported by the medical team received more hospice care in comparison with those not supported (adjusted odds ratio [AOR] = 3.53; 95% CI, 1.53 to 8.12, P = .003). High religious coping patients whose spiritual needs were largely or completely supported were more likely to receive hospice (AOR = 4.93; 95% CI, 1.64 to 14.80; P = .004) and less likely to receive aggressive care (AOR = 0.18; 95% CI, 0.04 to 0.79; P = .02) in comparison with those not supported. Spiritual support from the medical team and pastoral care visits were associated with higher QOL scores near death (20.0 [95% CI, 18.9 to 21.1] v 17.3 [95% CI, 15.9 to 18.8], P = .007; and 20.4 [95% CI, 19.2 to 21.1] v 17.7 [95% CI, 16.5 to 18.9], P = .003, respectively). Support of terminally ill patients' spiritual needs by the medical team is associated with greater hospice utilization and, among high religious copers, less aggressive care at EoL. Spiritual care is associated with better patient QoL near death.


Iron release from haemosiderin and ferritin by therapeutic and physiological chelators.
Iron release from both human and horse spleen haemosiderin to desferrioxamine was substantially less than that released from ferritin samples. This finding contradicts a previous report [Kontoghiorges, Chambers & Hoffbrand (1987) Biochem. J. 241, 87-92]. Differences in phosphate content of cores and in core size between haemosiderin and ferritin did not account for the different iron-release rates. Iron released to acetate was found to stimulate lipid peroxidation in liposomes, whereas that released to stronger chelators such as citrate and desferal did not. Absorption spectra and gel-filtration studies suggest that the acetate-solubilized iron was in the form of low-molecular-mass (less than 5 kDa) ferrihydrite fragments.


A human type 1 diabetes susceptibility locus maps to chromosome 21q22.3.
The Type 1 Diabetes Genetics Consortium (T1DGC) has assembled and genotyped a large collection of multiplex families for the purpose of mapping genomic regions linked to type 1 diabetes. In the current study, we tested for evidence of loci associated with type 1 diabetes utilizing genome-wide linkage scan data and family-based association methods. A total of 2,496 multiplex families with type 1 diabetes were genotyped with a panel of 6,090 single nucleotide polymorphisms (SNPs). Evidence of association to disease was evaluated by the pedigree disequilibrium test. Significant results were followed up by genotyping and analyses in two independent sets of samples: 2,214 parent-affected child trio families and a panel of 7,721 case and 9,679 control subjects. RESULTS- Three of the SNPs most strongly associated with type 1 diabetes localized to previously identified type 1 diabetes risk loci: INS, IFIH1, and KIAA0350. A fourth strongly associated SNP, rs876498 (P = 1.0 x 10(-4)), occurred in the sixth intron of the UBASH3A locus at chromosome 21q22.3. Support for this disease association was obtained in two additional independent sample sets: families with type 1 diabetes (odds ratio [OR] 1.06 [95% CI 1.00-1.11]; P = 0.023) and case and control subjects (1.14 [1.09-1.19]; P = 7.5 x 10(-8)). The T1DGC 6K SNP scan and follow-up studies reported here confirm previously reported type 1 diabetes associations at INS, IFIH1, and KIAA0350 and identify an additional disease association on chromosome 21q22.3 in the UBASH3A locus (OR 1.10 [95% CI 1.07-1.13]; P = 4.4 x 10(-12)). This gene and its flanking regions are now validated targets for further resequencing, genotyping, and functional studies in type 1 diabetes.


[Evaluation of the quality of information about pregnancy found in webpages according to the Peruvian guidelines].
The objective of this study is to evaluate the information quality about pregnancy symptoms in Spanish available in the internet. This is an analytic, cross-sectional study. In order to evaluate the selected websites, we used a methodology previously validated by Curró et al. The websites were selected from Google, MSN.com and Yahoo.com. The quality evaluation included three components: medical contents, accountability and usability of the website. The medical content was compared with the data available in the national guidelines for Comprehensive Sexual and Reproductive Health, from the Peruvian Ministry of Health. Ninety nine websites in Spanish were evaluated. From them, 26.3% had medium adherence to the gold standard document. In 37.4% the websites were of low quality. A total of 24.2% were blogs, they were associated (as a protrective factor) to sites of poor quality (OR: 0.1, 95% CI: 0.02 to 0.5). The majority of websites in Spanish related to pregnancy symptoms have low quality. These findings indicate the need to properly educate patients and general public, and a critical evaluation of the information quality found at the Internet as well.


Effect of annealing treatments on photoluminescence and charge storage mechanism in silicon-rich SiNx:H films.
In this study, a wide range of a-SiNx:H films with an excess of silicon (20 to 50%) were prepared with an electron-cyclotron resonance plasma-enhanced chemical vapor deposition system under the flows of NH3 and SiH4. The silicon-rich a-SiNx:H films (SRSN) were sandwiched between a bottom thermal SiO2 and a top Si3N4 layer, and subsequently annealed within the temperature range of 500-1100°C in N2 to study the effect of annealing temperature on light-emitting and charge storage properties. A strong visible photoluminescence (PL) at room temperature has been observed for the as-deposited SRSN films as well as for films annealed up to 1100°C. The possible origins of the PL are briefly discussed. The authors have succeeded in the formation of amorphous Si quantum dots with an average size of about 3 to 3.6 nm by varying excess amount of Si and annealing temperature. Electrical properties have been investigated on Al/Si3N4/SRSN/SiO2/Si structures by capacitance-voltage and conductance-voltage analysis techniques. A significant memory window of 4.45 V was obtained at a low operating voltage of ± 8 V for the sample containing 25% excess silicon and annealed at 1000°C, indicating its utility in low-power memory devices.


Interventions for supporting informal caregivers of patients in the terminal phase of a disease.
Patients in the terminal phase of a disease may have complex needs. It is often family and friends who play a central role in providing support, despite health professional input and regardless of whether the patient is at home or elsewhere. Such informal caring may involve considerable physical, psychological, and economic stresses. A range of supportive programmes for caregivers is being developed including psychological support and practical assistance. To assess the effects of supportive interventions that aim to improve the psychological and physical health of informal caregivers of patients in the terminal phase of their illness. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2 2010); MEDLINE (1950 to May 2010); EMBASE (1980 to May 2010); PsycINFO (1872 to May 2010); CINAHL (1937 to May 2010); National Health Service Research Register (2000 to November 2008) and Dissertation Abstracts (1716 to May 2010). We searched the reference lists of relevant studies; contacted experts; and handsearched journals. Randomised controlled trials (RCTs) of interventions to support adults who were caring for a friend or relative with a disease in the terminal phase. Interventions could include practical and emotional support and/or the facilitation of coping skills. Interventions could support caregivers indirectly via patient care. Two authors independently screened citations against the selection criteria. Data were extracted by one author and checked by another. This included extraction of any adverse effects. Risk of bias assessment was undertaken by two authors. We contacted trial authors to obtain missing information. Trial data were combined, where appropriate, on the review's primary outcomes. We included eleven RCTs involving 1836 caregiver participants. Nine interventions were delivered directly to the caregiver. Seven of these provided support in the caring role, another involved a family life review, and one grief therapy. None provided practical support. The other two interventions aimed to support caregivers indirectly via patient care. Overall the risk of bias is unclear, as all trials under-reported methods.There is low quality evidence that interventions directly supporting the caregiver significantly reduce psychological distress in the short term (8 trials: standardised mean difference (SMD) -0.15; 95% confidence interval (CI) -0.28 to -0.02). There is also low quality evidence that these interventions in the short term may marginally improve coping skills and quality of life, but neither results were statistically significant (7 trials: SMD -0.05; 95% CI -0.24 to 0.14; 6 trials: SMD 0.08; 95% CI -0.11 to 0.26, respectively). One study assessed physical outcomes, specifically sleep improvement, and found no difference (median effect 0.00). No study measured health service use or adverse outcomes. In one study, however, a subgroup of intervention participants had higher levels of family conflict.Evidence was less clear on the indirect interventions. While both trials in this category found that supporting the patient may reduce psychological distress, none of the four assessments were statistically significant. There were no evaluations of coping with the caring role, quality of life, service use or adverse outcomes. In one trial there was no difference between trial arms in the proportion of caregivers reporting good physical health. There is evidence that supportive interventions may help reduce caregivers' psychological distress. These findings suggest that practitioners should enquire about the concerns of caregivers and should consider that they may benefit from additional support. There is, however, a need for further research to explore the benefits identified, and to assess the interventions' effects on physical health, and potential harms. Trials need to report their methods fully.


Severe dry eye syndrome after radiotherapy for head-and-neck tumors.
To investigate the incidence of severe dry eye syndrome (DES) after external beam radiotherapy for head-and-neck cancer and its dependence on the parameters relevant to external beam radiotherapy. The present retrospective study included 78 patients treated for primary extracranial head-and-neck tumors between 1965 and 2000, whose lacrimal apparatus/entire globe was exposed to fractionated external beam radiotherapy. The dose received by the major lacrimal gland was used for analysis. The end point of the present study was the ophthalmologic diagnosis of severe DES leading to vision compromise. Of the 78 patients, 40 developed severe DES leading to visual compromise. The incidence of DES increased steadily from 6% at 35-39.99 Gy to 50% at 45-49.99 Gy and 90% at 60-64.99 Gy. With a mean of 0.9 years (range, 1 month to 3 years), the latency of DES was observed to be a function of the total dose and the dose per fraction. On univariate and multivariate analysis, the total dose (p < .0001 and p < .0001, respectively) and dose per fraction (p ≤ .0001 and p = .0044, respectively) were significant. However, age, gender, and the use of chemoradiotherapy were not. The actuarial analysis indicated a 5-year probability of freedom from DES of 93% for doses <45 Gy, 29% for 45-59.9 Gy, and 3% doses ≥60 Gy. A logistic normal tissue complication probability model fit to our data obtained a dose of 34 and 38 Gy corresponding to a 5% and 10% incidence of DES. With a dose of 34 Gy corresponding to a 5% incidence of DES, the risk of severe DES increased, and the latency decreased with an increase in the total dose and dose per fraction to the lacrimal gland. The effect of chemoradiotherapy and hyperfractionation on the risk of DES needs additional investigation.


The Moderate Alcohol and Cardiovascular Health Trial (MACH15): Design and methods for a randomized trial of moderate alcohol consumption and cardiometabolic risk.
Observational studies have documented lower risks of coronary heart disease and diabetes among moderate alcohol consumers relative to abstainers, but only a randomized clinical trial can provide conclusive evidence for or against these associations. The purpose of this study was to describe the rationale and design of the Moderate Alcohol and Cardiovascular Health Trial, aimed to assess the cardiometabolic effects of one alcoholic drink daily over an average of six years among adults 50 years or older. This multicenter, parallel-arm randomized trial was designed to compare the effects of one standard serving (∼11-15 g) daily of a preferred alcoholic beverage to abstention. The trial aimed to enroll 7800 people at high risk of cardiovascular disease. The primary composite endpoint comprised time to the first occurrence of non-fatal myocardial infarction, non-fatal ischemic stroke, hospitalized angina, coronary/carotid revascularization, or total mortality. The trial was designed to provide >80% power to detect a 15% reduction in the risk of the primary outcome. Secondary outcomes included diabetes. Adverse effects of special interest included injuries, congestive heart failure, alcohol use disorders, and cancer. We describe the design, governance, masking issues, and data handling. In three months of field center activity until termination by the funder, the trial randomized 32 participants, successfully screened another 70, and identified ∼400 additional interested individuals. We describe a feasible design for a long-term randomized trial of moderate alcohol consumption. Such a study will provide the highest level of evidence for the effects of moderate alcohol consumption on cardiovascular disease and diabetes, and will directly inform clinical and public health guidelines.


Fetal villosity and microvasculature of the bovine placentome in the second half of gestation.
The architecture of the fetal villous tree and its vasculature in the bovine placentome were studied in the second half of gestation using both conventional histology and histology of ink-filled blood vessels. These were compared with corrosion casts of plastic fillings of the vasculature, prepared for scanning electron microscopy. This combination of morphological methods allows perception of the villous tree throughout gestation from broad-conical to tall-conical form where branch ramification occurs mainly at right angles to the stem. The stem villus typically contains a single central artery and several peripheral veins arranged in parallel. The proximal branches to the stem, the intermediate villi, contain a central arteriole and accompanying venules. The distal branches, the terminal villi, enclose capillary convolutions which consist of an afferent arterial capillary limb, capillary loops and efferent venous capillary limbs. Vascular interconnections exist within the terminal villi, as capillaries or venules between the capillary convolutions, serially bridging them in up to 5 places, and as capillary anastomoses between the capillary loops. Coiling and sinusoidal dilatations of these loops develop near the end of gestation. The intraplacentomal rearrangement of villous trees with progressive gestation and their morphological vascular adaptations are discussed in relation to placental function, including the ever increasing need for transplacental substance exchange. This adaptation allows the blood to traverse the shortest possible arterioarteriolar route to the periphery of the trees where exchange takes place. The need for an increasing blood flow stimulates capillary growth and at the same time optimises the blood flow reaching the placental barrier represented by the vessel cast surface. The capillaries also carry the blood back into the very voluminous system of venules and veins where back diffusion may occur. The total volume of terminal villi of bovine placentome, the 'working part' of villous trees, hence distinctly increases with respect to the stem and intermediate villi, the 'supplying part' of the villous tree. In morphological terms the efficiency of the bovine transplacental diffusional exchange is higher than in the closely related 'co-ruminants' sheep and goats and distinctly higher when compared with the human placenta.


Pictorial review of colonic polyp and mass distortion and recognition with the CT virtual dissection technique.
Virtual dissection is a three-dimensional (3D) display technique for CT colonography that could potentially reduce interpretation times. With virtual dissection, the 3D model of the colon is "sliced" open along a centerline trace, rendering a 360° view of the endoluminal mucosa as a rectangular image. However, one must be familiar with several pitfalls and limitations to avoid errors in interpretation. One of the main limitations is the anatomic distortion that results. Polyp shape and colonic folds can be distorted and colonic or polyp mobility can lead to mischaracterization of polyps. Distorted folds, which frequently occur at flexures, can mimic polyps. Annular constricting masses can lead to skip areas, where the abnormality is not displayed. Various entities including diverticula and stool can mimic polyps at virtual dissection. Finally, technical errors such as an inadequate centerline trace can render a polyp occult. The purpose of this review is to demonstrate the spectrum of appearances of polyps at virtual dissection, with an emphasis on more difficult to detect polyps. In addition, 10 interactive virtual dissection quiz cases are presented along with corresponding two-dimensional and 3D endoluminal fly-through views.


CFTR is required for PKA-regulated ATP sensitivity of Kir1.1 potassium channels in mouse kidney.
The cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel plays vital roles in fluid transport in many epithelia. While CFTR is expressed along the entire nephron, its function in renal tubule epithelial cells remains unclear, as no specific renal phenotype has been identified in cystic fibrosis. CFTR has been proposed as a regulator of the 30 pS, ATP-sensitive renal K channel (Kir1.1, also known as renal outer medullar K [ROMK]) that is critical for K secretion by cells of the thick ascending limb (TAL) and distal nephron segments responsive to aldosterone. We report here that both ATP and glibenclamide sensitivities of the 30 pS K channel in TAL cells were absent in mice lacking CFTR and in mice homozygous for the deltaF508 mutation. Curcumin treatment in deltaF508-CFTR mice partially reversed the defect in ATP sensitivity. We demonstrate that the effect of CFTR on ATP sensitivity was abrogated by increasing PKA activity. We propose that CFTR regulates the renal K secretory channel by providing a PKA-regulated functional switch that determines the distribution of open and ATP-inhibited K channels in apical membranes. We discuss the potential physiological role of this functional switch in renal K handling during water diuresis and the relevance to renal K homeostasis in cystic fibrosis.


Hiring for smarts.
Yes, it's nice when a leader is charismatic and confident. And a great resume can tell you a lot about a person's knowledge and experience. But such assets are no substitute for sheer business intelligence, and they reveal very little about a leader's ability to consistently reach the "right" answer. How can hiring managers flag individuals with such smarts? Historically, the only reliable measure of brainpower has been the standard IQ test, which is rarely used in business settings because of the specific subjects it tests for-math, reading, and spatial reasoning-and because of its multiple-choice format. Despite its shortcomings, the standard IQ test is still a better predictor of managerial success than any other assessment tool companies currently use, Justin Menkes argues. It's true that there isn't a version of IQ testing that applies to the corporate world, but in rejecting IQ tests altogether, hiring managers have thwarted their own attempts to identify true business stars. The author defines the specific subjects that make up "executive intelligence"-namely, accomplishing tasks, working with people, and judging oneself. He describes how to formulate questions to test job candidates for their mastery of these subjects, offering several examples based on real situations. Knowledge questions, such as those used in standard behavioral interviews, require people to recite what they have learned or experienced; intelligence questions call for individuals to demonstrate their abilities. Therefore, the questions in an executive intelligence test shouldn't require specific industry expertise or experience; any knowledge they call for must be rudimentary and common to all executives. And the questions should not be designed to ask whether the candidate has a particular skill; they should be configured so that the candidate will have to demonstrate that skill in the course of answering them.


Propionyl-L-carnitine improves postischemic blood flow recovery and arteriogenetic revascularization and reduces endothelial NADPH-oxidase 4-mediated superoxide production.
The beneficial effect of the natural compound propionyl-l-carnitine (PLC) on intermittent claudication in patients with peripheral arterial disease is attributed to its anaplerotic function in ischemic tissues, but inadequate information is available concerning action on the vasculature. We investigated the effects of PLC in rabbit hind limb collateral vessels after femoral artery excision, mouse dorsal air pouch, chicken chorioallantoic membrane, and vascular cells by angiographic, Doppler flow, and histomorphometrical and biomolecular analyses. PLC injection accelerated hind limb blood flow recovery after 4 days (P<0.05) and increased angiographic quadriceps collateral vascularization after 7 days (P<0.001) Histomorphometry confirmed the increased vascular area (P<0.05), with unchanged intramuscular capillary density. PLC-induced dilatative adaptation, and growth was found associated with increased inducible nitric oxide synthase and reduced arterial vascular endothelial growth factor and intracellular adhesion molecule-1 expression. PLC also increased vascularization in air pouch and chorioallantoic membrane (P<0.05), particularly in large vessels. PLC increased endothelial and human umbilical vascular endothelial cell proliferation and rapidly reduced inducible nitric oxide synthase and NADPH-oxidase 4-mediated reactive oxygen species production in human umbilical vascular endothelial cells; NADPH-oxidase 4 also regulated NF-kappaB-independent intracellular adhesion molecule-1 expression. Our results provided strong evidence that PLC improves postischemic flow recovery and revascularization and reduces endothelial NADPH-oxidase-related superoxide production. We recommend that PLC should be included among therapeutic interventions that target endothelial function.


Evaluation of binding in a transfected cell line expressing a peripheral cannabinoid receptor (CB2): identification of cannabinoid receptor subtype selective ligands.
Two cannabinoid receptors have been identified to date; one is located predominantly in the central nervous system (CB1), whereas the other is located exclusively in the periphery (CB2). The purposes of this study were to explore further the binding requirements of the CB2 receptor and to search for compounds displaying distinct affinities for either cannabinoid receptor. The binding affinities of a series of cannabinoids tested previously at the CB1 receptor were determined at cloned human CB1 and CB2 receptors using a filtration assay. In addition, possible allosteric regulation of the CB2 receptor was examined. Sodium and a GTP analog elicited a concentration-dependent decrease in specific binding to the CB2 receptor. The affinity of cannabinol for CB2 receptors (Ki = 96.3 +/- 14 nM) was confirmed to be in approximately the same range as that of delta 9-THC (Ki = 36.4 +/- 10 nM). Affinities at cloned CB1 and CB2 receptors were compared with affinities determined in the brain. Although most of the chosen compounds did not discriminate between CB1 and CB2, several ligands were identified that showed selectivity. Affinity ratios demonstrated that two 2'-fluoro analogs of anandamide were over 23-fold selective for the CB1 receptor and confirmed the CB1 selectivity of SR141716A {N- (piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carboxamidehydrochloride}. In addition, WIN-55, 212-2 {(R)-(+)-[2, 3-dihydro-5-methyl-3-[(4-morpholinyl) methyl] pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthalenyl) methanone} and a closely related propyl indole analog were shown to be 6.75- and 27.5- fold selective, respectively, for the CB2 receptor. These ligands can now serve as a basis for the design of compounds with even greater selectivity.


A novel method of differential gene expression analysis using multiple cDNA libraries applied to the identification of tumour endothelial genes.
In this study, differential gene expression analysis using complementary DNA (cDNA) libraries has been improved. Firstly by the introduction of an accurate method of assigning Expressed Sequence Tags (ESTs) to genes and secondly, by using a novel likelihood ratio statistical scoring of differential gene expression between two pools of cDNA libraries. These methods were applied to the latest available cell line and bulk tissue cDNA libraries in a two-step screen to predict novel tumour endothelial markers. Initially, endothelial cell lines were in silico subtracted from non-endothelial cell lines to identify endothelial genes. Subsequently, a second bulk tumour versus normal tissue subtraction was employed to predict tumour endothelial markers. From an endothelial cDNA library analysis, 431 genes were significantly up regulated in endothelial cells with a False Discovery Rate adjusted q-value of 0.01 or less and 104 of these were expressed only in endothelial cells. Combining the cDNA library data with the latest Serial Analysis of Gene Expression (SAGE) library data derived a complete list of 459 genes preferentially expressed in endothelium. 27 genes were predicted tumour endothelial markers in multiple tissues based on the second bulk tissue screen. This approach represents a significant advance on earlier work in its ability to accurately assign an EST to a gene, statistically measure differential expression between two pools of cDNA libraries and predict putative tumour endothelial markers before entering the laboratory. These methods are of value and available http://www.compbio.ox.ac.uk/data/diffex.html to researchers that are interested in the analysis of transcriptomic data.


Mimicking bone extracellular matrix: integrin-binding peptidomimetics enhance osteoblast-like cells adhesion, proliferation, and differentiation on titanium.
Interaction between the surface of implants and biological tissues is a key aspect of biomaterials research. Apart from fulfilling the non-toxicity and structural requirements, synthetic materials are asked to direct cell response, offering engineered cues that provide specific instructions to cells. This work explores the functionalization of titanium with integrin-binding peptidomimetics as a novel and powerful strategy to improve the adhesion, proliferation and differentiation of osteoblast-like cells to implant materials. Such biomimetic strategy aims at targeting integrins αvβ3 and α5β1, which are highly expressed on osteoblasts and are essential for many fundamental functions in bone tissue development. The successful grafting of the bioactive molecules on titanium is proven by contact angle measurements, X-ray photoelectron spectroscopy and fluorescent labeling. Early attachment and spreading of cells are statistically enhanced by both peptidomimetics compared to unmodified titanium, reaching values of cell adhesion comparable to those obtained with full-length extracellular matrix proteins. Moreover, an increase in alkaline phosphatase activity, and statistically higher cell proliferation and mineralization are observed on surfaces coated with the peptidomimetics. This study shows an unprecedented biological activity for low-molecular-weight ligands on titanium, and gives striking evidence of the potential of these molecules to foster bone regeneration on implant materials.


Polymers and hydrogels for local nucleic acid delivery.
The potential of gene therapy for the treatment for chronic and life-threatening diseases has been seen for a long time, but widespread applications are still hampered by the difficulties to deliver the highly charged and large nucleic acid molecules to their intracellular targets. More recently, investigators have been aiming for local delivery of nucleic acids mostly by the use of hydrogels. In this way, in vivo efficacy can be enhanced by avoiding the target transport challenges and at the same time limit off-target effects. In these systems, nucleic acids are entrapped within hydrogels, either as conjugates or as polyplex particles, for local and controlled release. There are numerous design features in the selection of polymers, for both particle and hydrogel formation that should be considered to achieve efficient local nucleic acid delivery. Therefore, this review focusses on the rational design of polymeric and hydrogel materials for local gene therapy applications.


Partner notification among men who have sex with men and heterosexuals with STI/HIV: different outcomes and challenges.
Partner notification effectiveness among index clients diagnosed with HIV, syphilis and/or gonorrhoea at sexually transmitted infection (STI) clinics was evaluated between 2010 and 2012. We explored percentages of identifiable, notified and tested partners by sexual preference and gender. Partner notification trends were studied using the national STI database. Men who have sex with men (n = 304), heterosexual men (n = 33) and women (n = 35) reported, respectively, 6.7, 3.8 and 2.3 partners per index. Percentages of identifiable partners differed between groups (men who have sex with men: 46%, heterosexual men: 63%, women: 87%, p < 0.001). The percentage of notified partners (of those identifiable) was lowest for heterosexual men (76%; men who have sex with men: 92%; women: 83%; p < 0.001). STI positivity rates among notified partners were high: 33%-50% depending on sexual preference. Among men who have sex with men, having HIV was associated with not notifying all identifiable partners. Percentages of notified clients at STI clinics increased between 2010 and 2012: from 13% to 19% among men who have sex with men, from 13% to 18% among heterosexual men and from 8% to 11% among women (p < 0.001 for all groups). The percentage of STI/HIV detected through partner notification increased among men who have sex with men (from 22% to 30%) and women (from 25% to 29%; p < 0.001). Unidentifiable partners among men who have sex with men, lower partner notification effectiveness for HIV and the relative large proportion of heterosexual men not notifying their partners appear to be important partner notification challenges.


High chloride content calcium silicate glasses.
Chloride is known to volatilize from silicate glass melts and until now, only a limited number of studies on oxychloride silicate glasses have been reported. In this paper we have synthesized silicate glasses that retain large amounts of CaCl2. The CaCl2 has been added to the calcium metasilicate composition (CaO·SiO2). Glasses were produced via a melt quench route and an average of 70% of the chloride was retained after melting. Up to 31.6 mol% CaCl2 has been successfully incorporated into these silicate glasses without the occurrence of crystallization. 29Si MAS-NMR spectra showed the silicon being present mainly as a Q2 silicate species. This suggests that chloride formed Cl-Ca(n) species, rather than Si-Cl bonds. Upon increasing the CaCl2 content, the Tg reduced markedly from 782 °C to 370 °C. Glass density and glass crystallization temperature decreased linearly with an increase in the CaCl2 content. However, both linear regressions revealed a breakpoint at a CaCl2 content just below 20 mol%. This might be attributed to a significant change in the structure and is also correlated with the nature of the crystallizing phases formed upon heat treatment. The glasses with less than 19.2 mol% CaCl2 crystallized to wollastonite, whilst the compositions with CaCl2 content equal to or greater than 19.2 mol% are thought to crystallize to CaCl2. In practice, the crystallization of CaCl2 could not occur until the crystallization temperature fell below the melting point of CaCl2. The implications of the results along with the high chloride retention are discussed.


Decarbonising energy: The developing international activity in hydrogen technologies and fuel cells.
Hydrogen technologies and fuel cells offer an alternative and improved solution for a decarbonised energy future. Fuel cells are electrochemical converters; transforming hydrogen (or energy sources containing hydrogen) and oxygen directly into electricity. The hydrogen fuel cell, invented in 1839, permits the generation of electrical energy with high efficiency through a non-combustion, electrochemical process and, importantly, without the emission of CO2 at its point of use. Hitherto, despite numerous efforts to exploit the obvious attractions of hydrogen technologies and hydrogen fuel cells, various challenges have been encountered, some of which are reviewed here. Now, however, given the exigent need to urgently seek low-carbon paths for humankind's energy future, numerous countries are advancing the deployment of hydrogen technologies and hydrogen fuel cells not only for transport, but also as a means of the storage of excess renewable energy from, for example, wind and solar farms. Furthermore, hydrogen is also being blended into the natural gas supplies used in domestic heating and targeted in the decarbonisation of critical, large-scale industrial processes such as steel making. We briefly review specific examples in countries such as Japan, South Korea and the People's Republic of China, as well as selected examples from Europe and North America in the utilization of hydrogen technologies and hydrogen fuel cells.


Faith as a resource in patients with multiple sclerosis is associated with a positive interpretation of illness and experience of gratitude/awe.
The aim of this cross-sectional anonymous survey with standardized questionnaires was to investigate which resources to cope were used by patients with multiple sclerosis (MS). We focussed on patients' conviction that their faith might be a strong hold in difficult times and on their engagement in different forms of spirituality. Consecutively 213 German patients (75% women; mean age 43 ± 11 years) were enrolled. Fifty-five percent regarded themselves as neither religious nor spiritual (R-S-), while 31% describe themselves as religious. For 29%, faith was a strong hold in difficult times. This resource was neither related to patients' EDSS scores, and life affections, fatigue, negative mood states, life satisfaction nor to Positive attitudes. Instead it was moderately associated with a Reappraisal strategy (i.e., and positive interpretation of illness) and experience of gratitude/awe. Compared to spiritual/religious patients, R-S- individuals had significantly (P < .0001) lower Reappraisal scores and lower engagement in specific forms of spiritual practices. The ability to reflect on what is essential in life, to appreciate and value life, and also the conviction that illness may have meaning and could be regarded as a chance for development was low in R-S- individuals which either may have no specific interest or are less willing to reflect these issues.


Aberration correction by nonlinear beam mixing: generation of a pseudo point sound source.
Nonlinear beam mixing with microbubbles was explored to create a pseudo point source for aberration correction of therapeutic ultrasound. A damping coefficient for a bubble driven by a dual frequency sound field was derived by revisiting Prosperetti's linearized damping model. As a result, the overall damping term for dual frequency was obtained by linear summation of two damping terms for each frequency. The numerical simulation based on the bubble model suggests that the most efficient size range to generate a 1 MHz frequency from 4 MHz and 5 MHz sound sources is 2.6 to 3.0 microm. Furthermore, this size range constitutes the primary distribution of a specific ultrasound contrast agent. When a chamber of 0.1% of the diluted agent is sonified by 4 MHz and 5 MHz sound beams with 80 degrees incident angle between them, an approximately 100 Pa, 1 MHz difference frequency signal can be measured approximately 10 cm away. In addition, the received 1 MHz difference frequency signal shows omni-directional characteristics, even though the overlap zone of the two sound beams is on the order of the difference frequency wavelength. Therefore, the induced sound source can be considered as a pseudo point source and is expected to be useful for aberration correction for therapeutic ultrasound.


Noninfectious Complications of Peritoneal Dialysis in Korean Children: A 26-Year Single-Center Study.
The aim of this study was to investigate noninfectious complications of peritoneal dialysis (PD), including mechanical and metabolic complications, at a single center in Korea. We analyzed data from 60 PD patients aged ≤18 years (40 boys and 20 girls) during the period between 1986 and 2012. The collected data included gender, age, causes of PD, incidence of noninfectious complications, and treatment for the complications. The mean duration of PD therapy was 28.7±42.1 months (range 1-240 months). The most common cause of end-stage renal disease was glomerular disease (43.3%). There were no statistically significant differences between patients with and without mechanical complications regarding gender, age at the start of PD, and total duration of PD. Outflow failure was the most common catheter-related complication (14.3%), followed by leakage (10.0%) and hernia (8.6%). Metabolic complications, such as hyperglycemia and hypokalemia, were observed in three of 16 patients. The frequency of noninfectious complications of PD in our study was comparable with those in previous pediatric studies. PD was switched to hemodialysis (HD) in only three patients. Our results indicate that noninfectious complications of PD are common, though they hardly lead to catheter removal or HD in pediatric patients on PD.


The increase of fatty acid-binding protein aP2 in overweight and obese children: interactions with dietary fat and impact on measures of subclinical inflammation.
In adults, circulating aP2 may link obesity, inflammation and the metabolic syndrome, but there are few data in children. Experimental models support that dietary factors, particularly dietary fat, may be major determinants of phenotype. The aim of this study was to investigate, in normal, overweight and obese children, the relationships among aP2, the metabolic syndrome, inflammation and diet. This was a cross-sectional study conducted in Northern Switzerland. Subjects for this study were 6- to 14-year-old, prepubertal and early pubertal, normal weight, overweight and obese children (n=124). Body mass index (BMI), body fat percent, waist-to-hip ratio, blood pressure, circulating aP2, fasting insulin, C-reactive protein (CRP), plasma lipids and dietary intakes of macro- and micronutrients were determined. Circulating aP2 markedly increased with increasing central and total adiposity, and predicted measures of insulin resistance. Independent of BMI standard deviation scores and puberty, aP2 correlated with intake of the antioxidant vitamins A, C and E as well as circulating concentrations of CRP, leptin and low-density lipoprotein cholesterol. Children with lower aP2 concentrations consuming high-fat diets did not show an increase in fasting insulin or CRP, whereas those with higher aP2 concentrations showed marked increases in these measures with high intakes of fat or saturated fat. Increased central and overall adiposity in children are associated with higher circulating aP2 concentrations. In children with high dietary intakes of total fat and saturated fat, but not those with low intakes, higher aP2 concentrations are associated with measures of insulin resistance and inflammation.


Yogurt improves insulin resistance and liver fat in obese women with nonalcoholic fatty liver disease and metabolic syndrome: a randomized controlled trial.
Because consumption of conventional yogurt has beneficial effects in a healthy population, and insulin resistance (IR) is the mutual pathogenesis in nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS), we hypothesized that yogurt would ameliorate IR in patients with NAFLD and MetS. The aim of this study was to investigate the effects of yogurt on IR and secondary endpoints including liver fat, gut microbiota, and serum biomarkers of inflammation and oxidative stress in obese women with NAFLD and MetS. One hundred obese women aged 36-66 y with both NAFLD and MetS were randomly assigned to consume 220 g/d of either conventional yogurt or milk for 24 wk. At baseline and week 24, we measured anthropometric indices, serum glucose, insulin, lipids, and cytokines in all participants, and liver fat and gut microbiota in 20 participants randomly selected from each group. Forty-eight participants from the yogurt group and 44 from the milk group completed the intervention. Compared with milk, yogurt significantly decreased the homeostasis model assessment of insulin resistance (-0.53; 95% CI: -1.03, -0.02), fasting insulin (-2.77 mU/L; 95% CI: -4.91, -0.63 mU/L), 2-h insulin (-25.5 mU/L; 95% CI: -33.0, -17.9 mU/L), 2-h area under the curve for insulin (-29.4 mU/L · h; 95% CI: -44.0, -14.8 mU/L · h), alanine aminotransferase (-4.65 U/L; 95% CI: -8.67, -0.64 U/L), intrahepatic lipid (-3.44%; 95% CI: -6.19%, -0.68%), and hepatic fat fraction (-3.48%; 95% CI: -6.34%, -0.63%). Yogurt also decreased serum LPS (-0.31 EU/mL; 95% CI: -0.48, -0.14 EU/mL), fibroblast growth factor 21 (-57.76 pg/mL; 95% CI: -86.32, -29.19 pg/mL), lipids, and biomarkers of inflammation and oxidative stress, and altered gut microbiota composition. Mediation analysis showed that yogurt may improve IR by reducing serum lipids, inflammation, oxidative stress, and LPS. Yogurt was better than milk at ameliorating IR and liver fat in obese Chinese women with NAFLD and MetS, possibly by improving lipid metabolism, reducing inflammation, oxidative stress, and LPS, and changing the gut microbiota composition. This trial was registered at www.chictr.org.cn as ChiCTR-IPR-15006801.


Endocrine remodelling of the adult intestine sustains reproduction in Drosophila.
The production of offspring is energetically costly and relies on incompletely understood mechanisms that generate a positive energy balance. In mothers of many species, changes in key energy-associated internal organs are common yet poorly characterised functionally and mechanistically. In this study, we show that, in adult Drosophila females, the midgut is dramatically remodelled to enhance reproductive output. In contrast to extant models, organ remodelling does not occur in response to increased nutrient intake and/or offspring demands, but rather precedes them. With spatially and temporally directed manipulations, we identify juvenile hormone (JH) as an anticipatory endocrine signal released after mating. Acting through intestinal bHLH-PAS domain proteins Methoprene-tolerant (Met) and Germ cell-expressed (Gce), JH signals directly to intestinal progenitors to yield a larger organ, and adjusts gene expression and sterol regulatory element-binding protein (SREBP) activity in enterocytes to support increased lipid metabolism. Our findings identify a metabolically significant paradigm of adult somatic organ remodelling linking hormonal signals, epithelial plasticity, and reproductive output.


Asparagus decline: Autotoxicity and autotoxic compounds in asparagus rhizomes.
Asparagus (Asparagus officinalis L.) is a perennial vegetable, but its crop productivity and quality decrease gradually. One possible reason for "asparagus decline" is thought to be the autotoxicity of asparagus. However, the autotoxic property of asparagus rhizomes remains unknown. The objective of this study was to determine the potential role of rhizomes in the autotoxicity of asparagus. An aqueous methanol extract of asparagus rhizomes inhibited the growth of asparagus seedlings and six other test plants in a concentration-dependent manners: garden cress (Lepidum sativum L.), lettuce (Lactuca sativa L.), alfalfa (Medicago sativa L.), ryegrass (Lolium multiflorum Lam.), timothy (Phleum pratense L.) and barnyardgrass (Echinochloa crus-galli (L.) Beauv.). These results suggest that asparagus rhizomes contain autotoxic compounds. The extract was purified through several chromatographic steps with monitoring the autotoxic activity, and p-coumaric acid and iso-agatharesinol were isolated. These compounds inhibited the shoot and root growth of asparagus and two other test plants, garden cress and ryegrass, at concentrations higher than 0.1mM. The concentrations required for 50% inhibition of the root and shoot growth of these test plants ranged from 0.36 to 0.85mM and 0.41-1.22mM for p-coumaric acid and iso-agatharesinol, respectively. Therefore, these compounds may contribute to the autotoxicity caused by asparagus rhizomes and may be involved in "asparagus decline".


Information excess in medicine. Overview, relevance to dermatology, and strategies for coping.
The amount of biomedical information contained in scientific journals has grown to the point that complete coverage of this material is impossible. The number of articles and journals being published has been growing at an exponential rate since 1750. Thirty-four thousand references from 4000 journals are added each month to the National Library of Medicine MEDLINE database from among the more than 100,000 scientific journals now published. This increase in scientific literature reflects not greater productivity but simply a larger number of scientists at work. Most articles written are eventually published in the medical literature, but a large number of scientific articles are of less than optimal quality, and most scientific articles that are published are never cited. Articles of higher quality and usefulness cluster in a few journals that enjoy great use in medical libraries and high scores on bibliometric scores such as the Science Citation Index. To assess the reading habits of dermatologic trainees and evaluate how they cope with this information excess, a survey was distributed to 36 residents in three training programs. The average number of medical journal reading hours per month was 17; the number of hours devoted to reading issues of the Archives of Dermatology, the Journal of the American Academy of Dermatology, and the Journal of Investigative Dermatology were 3.2, 5.0, and 1.4, respectively; and the average resident read seven peer-reviewed journals, two to four dermatologic tabloids, and four peer-reviewed medical journals. Critically and consistently reading a limited number of high-quality peer-reviewed journals as well as taking advantage of information available through computer networks and bibliographic and full-text databases is the best approach to coping with the volume of medical literature. Translating this information into a change in attitude and modification of physician behavior is best accomplished when local role models incorporate new ideas into their practice and teaching. Modifications that would, in fact, bring about truly useful changes, such as decreasing the number of new publications, melding journals already present into smaller numbers of publications rather than instituting new journals, altering the "publish-or-perish" rules, and writing more comprehensive articles rather than multiple small contributions, all await fundamental alterations in long-accepted policies in medicine.


Independent and cooperative motions of the Kv1.2 channel: voltage sensing and gating.
Voltage-gated potassium (Kv) channels, such as Kv1.2, are involved in the generation and propagation of action potentials. The Kv channel is a homotetramer, and each monomer is composed of a voltage-sensing domain (VSD) and a pore domain (PD). We analyzed the fluctuations of a model structure of Kv1.2 using elastic network models. The analysis suggested a network of coupled fluctuations of eight rigid structural units and seven hinges that may control the transition between the active and inactive states of the channel. For the most part, the network is composed of amino acids that are known to affect channel activity. The results suggested allosteric interactions and cooperativity between the subunits in the coupling between the motion of the VSD and the selectivity filter of the PD, in accordance with recent empirical data. There are no direct contacts between the VSDs of the four subunits, and the contacts between these and the PDs are loose, suggesting that the VSDs are capable of functioning independently. Indeed, they manifest many inherent fluctuations that are decoupled from the rest of the structure. In general, the analysis suggests that the two domains contribute to the channel function both individually and cooperatively.


Combining immunotherapy and radiation therapy for small cell lung cancer and thymic tumors.
Recent work with immunotherapy has shown promising results with treatment of several solid malignancies, and there are several reports of good systemic responses with the combination of immunotherapy and radiation therapy (RT), most notably in advanced melanoma. Given the rapid increase in the use of checkpoint blockade as well as anti-tumor vaccines, we review here the preclinical rationale and ongoing clinical work in combining immunotherapy with RT for small cell lung cancer (SCLC) and thymic tumors. While there are several reports of promising results with the combination of immunotherapy and conventional systemic treatment, we focus here on the ongoing clinical studies that combine immunotherapy with RT, and highlight the emerging data for this multimodality approach as well as key preclinical and clinical issues that remain to be addressed. With regards to SCLC, trials exploring to the combination of immunotherapy and RT are already ongoing, but clinical studies for this combination in thymoma are lacking.


Systematic review: worldwide variation in the frequency of coeliac disease and changes over time.
Coeliac disease (CD), originally thought to be largely confined to Northern Europe and Australasia and uncommon in North America and the Middle East, is now recognised to be equally common in all these countries. It is still thought to be rare in the Orient and Sub-Saharan Africa. To assess geographical differences and time trends in the frequency of CD. Medline and Embase searches were conducted on 10 November 2012, from 1946 and 1980 respectively, using the key words: coeliac disease or celiac disease + prevalence or incidence or frequency. There were significant intra- and inter-country differences in the prevalence and incidence of CD. Only 24 ethnic Chinese and Japanese patients have been reported in the English literature. Of CD-associated HLA DQ antigens, DQ2 occurs in 5-10% of Chinese and sub-Saharan Africans, compared to 5-20% in Western Europe. DQ8 occurs in 5-10% of English, Tunisians and Iranians, but in <5% of Eastern Europeans, Americans and Asians. The prevalence and incidence of both clinically and serologically diagnosed CD increased in recent years. These geographical and temporal differences seem genuine, although variable indices of suspicion and availability of diagnostic facilities are confounding factors. Coeliac disease is increasing in frequency, with significant geographical differences. Although few cases have been described to date in the Orient and Sub-Saharan Africa, there is a significant prevalence of HLA DQ2 and wheat consumption is of the same order as that in Western Europe. CD may therefore become more common in the future in these countries.


Characteristics of youth soccer players aged 13-15 years classified by skill level.
To evaluate the growth, maturity status and functional capacity of youth soccer players grouped by level of skill. The sample included 69 male players aged 13.2-15.1 years from clubs that competed in the highest division for their age group. Height and body mass of players were measured and stage of pubic hair (PH) was assessed at clinical examination. Years of experience in football were obtained at interview. Three tests of functional capacity were administered: dash, vertical jump and endurance shuttle run. Performances on six soccer-specific tests were converted to a composite score which was used to classify players into quintiles of skill. Multiple analysis of covariance, controlling for age, was used to test differences among skill groups in experience, growth status and functional capacity, whereas multiple linear regression analysis was used to estimate the relative contributions of age, years of training in soccer, stage of PH, height, body mass, the height x weight interaction and functional capacities to the composite skill score. The skill groups differed significantly in the intermittent endurance run (p<0.05) but not in the other variables. Only the difference between the highest and lowest skill groups in the endurance shuttle run was significant. Most players in the highest (12 of 14) and high (11 of 14) skill groups were in stages PH 4 and PH 5. Pubertal status and height accounted for 21% of the variance in the skill score; adding aerobic resistance to the regression increased the variance in skill accounted for to 29%. In both regressions, the coefficient for height was negative. Adolescent soccer players aged 13-15 years classified by skill do not differ in age, experience, body size, speed and power, but differ in aerobic endurance, specifically at the extremes of skill. Stage of puberty and aerobic resistance (positive coefficients) and height (negative coefficient) are significant predictors of soccer skill (29% of the total explained variance), highlighting the inter-relationship of growth, maturity and functional characteristics of youth soccer players.


The role of the LAT-PLC-gamma1 interaction in T regulatory cell function.
The interaction between the linker for activation of T cells (LAT) with PLC-gamma1 is important for TCR-mediated Ca(2+) signaling and MAPK activation. Knock-in mice harboring a mutation at the PLC-gamma1 binding site (Y136) of LAT develop a severe lymphoproliferative syndrome. These mice have defective thymic development and selection and lack natural regulatory T cells, implicating a breakdown of both central and peripheral tolerance. To bypass this developmental defect, we developed a conditional knock-in line in which only LATY136F is expressed in mature T cells after deletion of the wild type LAT allele. Analysis of LATY136F T cells indicated that the interaction between LAT and PLC-gamma1 plays an important role in TCR-mediated signaling, proliferation, and IL-2 production. Furthermore, the deletion of LAT induced development of the lymphoproliferative syndrome in these mice. Although Foxp3(+) natural Treg cells were present in these mice after deletion, they were unable to suppress the proliferation of conventional T cells. Our data indicate that the binding of LAT to PLC-gamma1 is essential for the suppressive function of CD4(+)CD25(+) regulatory T cells.


Exploration of the HIF-1α/p300 interface using peptide and Adhiron phage display technologies.
The HIF-1α/p300 protein-protein interaction plays a key role in tumor metabolism and thus represents a high value target for anticancer drug-development. Although several studies have identified inhibitor candidates using rationale design, more detailed understanding of the interaction and binding interface is necessary to inform development of superior inhibitors. In this work, we report a detailed biophysical analysis of the native interaction with both peptide and Adhiron phage display experiments to identify novel binding motifs and binding regions of the surface of p300 to inform future inhibitor design.


N250 ERP correlates of the acquisition of face representations across different images.
We used ERPs to investigate neural correlates of face learning. At learning, participants viewed video clips of unfamiliar people, which were presented either with or without voices providing semantic information. In a subsequent face-recognition task (four trial blocks), learned faces were repeated once per block and presented interspersed with novel faces. To disentangle face from image learning, we used different images for face repetitions. Block effects demonstrated that engaging in the face-recognition task modulated ERPs between 170 and 900 msec poststimulus onset for learned and novel faces. In addition, multiple repetitions of different exemplars of learned faces elicited an increased bilateral N250. Source localizations of this N250 for learned faces suggested activity in fusiform gyrus, similar to that found previously for N250r in repetition priming paradigms [Schweinberger, S. R., Pickering, E. C., Jentzsch, I., Burton, A. M., & Kaufmann, J. M. Event-related brain potential evidence for a response of inferior temporal cortex to familiar face repetitions. Cognitive Brain Research, 14, 398-409, 2002]. Multiple repetitions of learned faces also elicited increased central-parietal positivity between 400 and 600 msec and caused a bilateral increase of inferior-temporal negativity (>300 msec) compared with novel faces. Semantic information at learning enhanced recognition rates. Faces that had been learned with semantic information elicited somewhat less negative amplitudes between 700 and 900 msec over left inferior-temporal sites. Overall, the findings demonstrate a role of the temporal N250 ERP in the acquisition of new face representations across different images. They also suggest that, compared with visual presentation alone, additional semantic information at learning facilitates postperceptual processing in recognition but does not facilitate perceptual analysis of learned faces.


Temperature-modulated diastereoselective transformations of 2-vinylindoles to tetrahydrocarbazoles and tetrahydrocycloheptadiindoles.
Direct and expedient access to densely substituted tetrahydrocarbazoles and tetrahydrocycloheptadiindoles bearing multiple contiguous stereocentres has been achieved via a two-fold divergent diastereoselective (dr up to >99 : 1) transformation of 2-vinylindoles. The high-yielding conversions (yield up to 87%) that are amenable for a wide range of substituted 2-vinylindoles proceed through Lewis acid-catalyzed [4 + 2] and [4 + 3] cyclization-aromatization cascade reactions, respectively, involving a heretofore-unprecedented reversal of the polarity (umpolung) of 2-vinylindoles. The two synthetic routes are effortlessly transposable into each other by merely modulating the temperature to furnish the corresponding products in a selective and exclusive fashion. In addition, another novel synthetic route to tetrahydroindolocarbazoles has been developed that advances via a formal [4 + 2] cyclization of 4-vinylindoles involving sequential C3 Michael addition-dearomatization-aromatization cascade reactions.


RNA Sequencing of Osteosarcoma Gene Expression Profile Revealed that miR-214-3p Facilitates Osteosarcoma Cell Proliferation via Targeting Ubiquinol-Cytochrome c Reductase Core Protein 1 (UQCRC1).
BACKGROUND Osteosarcoma (OS) is a common primary malignant bone tumor for which the molecular mechanisms remain unclear. Studies on coding and non-coding RNAs are needed to determine the molecular mechanism. MATERIAL AND METHODS To explore the potential roles of miRNAs and mRNA in OS, we determined the miRNA and mRNA expression profile of 3 pairs of OS and paracancerous tissues from patients with OS by sequencing and bioinformatics analysis. The expression levels of critical miRNAs and mRNAs were verified in 10 pairs of OS and paracancerous tissues. An miRNA inhibitor and mimics were used to investigate the interactions between miRNAs and target genes. The cell counting kit-8 assay was performed to evaluate OS cell proliferation after miRNA interference. RESULTS A total of 184 miRNAs and 2501 mRNAs were identified (fold-change >2.0 or <2.0, P<0.05), with up-regulation of 82 miRNAs and 1320 mRNAs and down-regulation of 102 miRNAs and 1181 mRNAs in OS tissue. The protein protein interaction network revealed that UQCRC1 (ubiquinol-cytochrome c reductase core protein 1) is a critical gene and a potential target gene of miR-214-3p. Both UQCRC1 and miR-214-3p were significantly differentially expressed in OS tissue and cell lines (down and up-regulated, respectively). Down-regulated miR-214-3p expression increased UQCRC1 expression and suppressed OS cell proliferation. In contrast, overexpression of miR-214-3p decreased UQCRC1 expression and promoted OS cell proliferation. CONCLUSIONS High miR-214-3p expression may promote OS cell proliferation by targeting UQCRC1, providing insight into a potential therapeutic target for preventing and treating OS.


Effect of semiquantitative culture results from complex host surgical wounds on dehiscence rates.
The primary aim of this study was to determine the effect of positive bacterial cultures at the time of closure on dehiscence rates. Pre- and post-débridement wound cultures from patients undergoing serial surgical débridement of infected wounds were compared with outcomes 30 days postoperatively. One-hundred patients were enrolled; 35 were excluded for incomplete culture data. Sixty-five patients were evaluated for species counts, including Coagulase negative Staphylococcus (CoNS), and semiquantitative culture data for each débridement. The post-débridement cultures on the date of closure had no growth in 42 patients (64.6%) of which 6 dehisced (14.3%), and 36 remained closed; with no statistically significant difference in dehiscence rates (p = 0.0664). Pre-débridement cultures from the 1st débridement of the 65 patients showed 8 patients had no growth, 29 grew 1 species, 19 grew 2 species, and 9 had 3-5 species. There was a reduction in the number of species and improvement of semiquantitative cultures with each subsequent débridement. The dehiscence rate for those who had 2 débridements (n = 42) was 21.4% at 30 day follow-up and 21.7% in those who had 3 débridements (n = 23). The number of débridements had no statistical significance on dehiscence rates. The presence of CoNS on the day of closure was a statistically significant risk for dehiscence within 30 days (p = 0.0091) postoperatively. This data demonstrates: (1) positive post-débridement cultures (scant/rare, growth in enrichment broth) at the time of closure did not affect overall dehiscence rates (p = 0.0664), (2) the number of species and semiquantitative culture results both improved with each subsequent débridement, (3) the number of surgical débridement did not influence postclosure dehiscence rates. (4) Positive cultures containing CoNS at the time of closure is a risk factor for dehiscence (p = 0.0091).


Determinants of adverse events in vascular surgery.
Patient safety is a national priority. Patient Safety Indicators (PSIs) monitor potential adverse events during hospital stays. Surgical specialty PSI benchmarks do not exist, and are needed to account for differences in the range of procedures performed, reasons for the procedure, and differences in patient characteristics. A comprehensive profile of adverse events in vascular surgery was created. The Nationwide Inpatient Sample was queried for 8 vascular procedures using ICD-9-CM codes from 2005 to 2009. Factors associated with PSI development were evaluated in univariate and multivariate analyses. A total of 1,412,703 patients underwent a vascular procedure and a PSI developed in 5.2%. PSIs were more frequent in female, nonwhite patients with public payers (p < 0.01). Patients at mid and low-volume hospitals had greater odds of developing a PSI (odds ratio [OR] = 1.17; 95% CI, 1.10-1.23 and OR = 1.69; 95% CI, 1.53-1.87). Amputations had highest PSI risk-adjusted rate and carotid endarterectomy and endovascular abdominal aortic aneurysm repair had lower risk-adjusted rate (p < 0.0001). PSI risk-adjusted rate increased linearly by severity of patient indication: claudicants (OR = 0.40; 95% CI, 0.35-0.46), rest pain patients (OR = 0.78; 95% CI, 0.69-0.90), ulcer (OR = 1.20; 95% CI, 1.07-1.34), and gangrene patients (OR = 1.85; 95% CI, 1.66-2.06). Patient safety events in vascular surgery were high and varied by procedure, with amputations and open abdominal aortic aneurysm repair having considerably more potential adverse events. PSIs were associated with black race, public payer, and procedure indication. It is important to note the overall higher rates of PSIs occurring in vascular patients and to adjust benchmarks for this surgical specialty appropriately.


General practitioners using complementary and alternative medicine differ from general practitioners using conventional medicine in their view of the risks of electromagnetic fields: a postal survey from Germany.
General practitioners (GPs) play a key role in consulting patients worried about health effects of electromagnetic fields (EMF). We compared GPs using conventional medicine (COM) with GPs using complementary and alternative medicine (CAM) concerning their perception of EMF risks. Moreover, we assessed whether the kind of alternative medicine has an influence on the results. A total of 2795 GPs drawn randomly from lists of German GPs were sent an either long or short self-administered postal questionnaire on EMF-related topics. Adjusted logistic regression models were fitted to assess the association of an education in alternative medicine with various aspects of perceiving EMF risks. Concern about EMF, misconceptions about EMF, and distrust toward scientific organizations are more prevalent in CAM-GPs. CAM-GPs more often falsely believed that mobile phone use can lead to head warming of more than 1°C (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.5-3.3), more often distrusted the Federal Office for Radiation Protection (OR = 2.2, 95% CI = 1.4-3.6), were more often concerned about mobile phone base stations (OR = 2.4, 95% CI = 1.6-3.6), more often attributed own health complaints to EMF (OR = 3.2, 95% CI = 1.8-5.6), and more often reported at least 1 EMF consultation (OR = 2.5, 95% CI = 1.6-3.9). GPs using homeopathy perceived EMF as more risky than GPs using acupuncture or naturopathic treatment. Concern about common EMF sources is highly prevalent among German GPs. CAM-GPs perceive stronger associations between EMF and health problems than COM-GPs. There is a need for evidence-based information about EMF risks for GPs and particularly for CAM-GPs. This is the precondition that GPs can inform patients about EMF and health in line with current scientific knowledge.


Coronavirus COV-19/SARS-CoV-2 affects women less than men: clinical response to viral infection.
CoV-19/SARS-CoV-2 is a highly pathogenic virus that causes coronavirus-19 disease (COVID-19) an acute respiratory distress syndrome which provokes serious problems for global health. Studies suggest that there are many differences between men and women in the immune response to CoV-19 infection and inflammatory diseases. Women, compared to men, are less susceptible to viral infections based on a different innate immunity, steroid hormones and factors related to sex chromosomes. The presence of two X chromosomes in women emphasize the immune system even if one is inactive. The immune regulatory genes encoded by X chromosome in female gender causes lower viral load levels, and less inflammation than in man, while CD4+ T cells are higher with better immune response. In addition, women generally produce higher levels of antibodies which remain in the circulation longer. The levels of activation of the immune cells are higher in women than in men, and it is correlated with the trigger of TLR7 and the production of IFN. TLR7 is higher in women than in men and its biallelic expression leads to higher immune responses and increases the resistance to viral infections. TLR7 is expressed in innate immune cells which recognizes single strand RNA virus by promoting the production of antibodies against the virus and the generation of pro-inflammatory cytokines including IL-6 and IL-1 family members. Moreover, in women the production of inflammatory IL-6 after viral infection is lower than in males and is often correlated with a better longevity. In addition, on the X chromosome there are loci that code for the genes involved in the regulation of immune cells such as FOXP3, and transcription factor for Treg involved in virus pathogenesis. The X chromosome influences the immune system by acting on many other proteins, including TLR8, CD40L and CXCR3 which can be over-expressed in women, and influence the response to viral infections and vaccinations. However, the biallelic expression of the X-linked genes can promote harmful autoimmune and inflammatory responses. Cardiovascular diseases are more frequent in males and subjects without cardiovascular dysfunctions infected by CoV-19 have a better prognosis, but these effects are still under study. It is hoped that certain drugs, such as CoV-19 receptor blockers, anti-inflammatories (against rheumatic diseases), monoclonal antibodies, anti-IL-1 and anti-IL-6, the remdesevir drug (analogue adenosine, effective against ebola), hydroxychloroquine (for the treatment of malaria) and vaccines, will open up new strategies and new therapeutic ways to combat this terrible virus.


Nesprin-3 regulates endothelial cell morphology, perinuclear cytoskeletal architecture, and flow-induced polarization.
Changes in blood flow regulate gene expression and protein synthesis in vascular endothelial cells, and this regulation is involved in the development of atherosclerosis. How mechanical stimuli are transmitted from the endothelial luminal surface to the nucleus is incompletely understood. The linker of nucleus and cytoskeleton (LINC) complexes have been proposed as part of a continuous physical link between the plasma membrane and subnuclear structures. LINC proteins nesprin-1, -2, and -4 have been shown to mediate nuclear positioning via microtubule motors and actin. Although nesprin-3 connects intermediate filaments to the nucleus, no functional consequences of nesprin-3 mutations on cellular processes have been described. Here we show that nesprin-3 is robustly expressed in human aortic endothelial cells (HAECs) and localizes to the nuclear envelope. Nesprin-3 regulates HAEC morpho-logy, with nesprin-3 knockdown inducing prominent cellular elongation. Nesprin-3 also organizes perinuclear cytoskeletal organization and is required to attach the centrosome to the nuclear envelope. Finally, nesprin-3 is required for flow-induced polarization of the centrosome and flow-induced migration in HAECs. These results represent the most complete description to date of nesprin-3 function and suggest that nesprin-3 regulates vascular endothelial cell shape, perinuclear cytoskeletal architecture, and important aspects of flow-mediated mechanotransduction.


Structure and expression of the c-sis gene and its relationship to sporadic meningiomas.
A deletion in an Alu repetitive sequence in the fifth intron of the c-sis gene of meningioma patients was previously described (M. Smidt et al., J. Clin. Invest., 86:1151-1157, 1990). The authors analyzed the structure of this intron in DNA from peripheral blood leukocytes and tumor samples of 86 patients with sporadic meningiomas. After amplifying these DNA sequences by the polymerase chain amplification reaction, the authors failed to find any cases with deletions. They also analyzed the effects on the expression of c-sis of the fifth intron with or without the deletion. A c-sis expression clone with an SV40 promoter was modified by adding introns 4, 5, and 6, and the resulting clones were used to examine the expression of c-sis mRNA in A172, NIH3T3, and Cos-7 cells. Northern blots showed that the quantity of message was not changed when the introns were present and that the size of the message was not changed by the deletion in the fifth intron. The effect of the fifth intron Alu sequence on the c-sis promoter was also tested using clones with chloramphenicol acetyltransferase as a reporter gene in A172 and Cos-7 cells. The c-sis promoter was not affected by the fifth intron Alu sequence with or without the deletion and in either orientation. There were also no effects when cells were stimulated by phorbol 12-myristate 13-acetate or the regulatory gene Tax from human T-lymphotropic virus type 1. These data do not support a role for deletions in the fifth c-sis intron in the development of most sporadic meningiomas.


Optical angular momentum conversion in a nanoslit.
We demonstrate partial conversion of circularly polarized light into orbital angular momentum-carrying vortex light with opposite-handed circular polarization. This conversion is accomplished in a novel manner using the birefringent properties of a circular subwavelength slit in a thin metal film. Our technique can be applied over a very wide range of frequencies and even allows the creation of anisotropic vortices when using a slit without circular symmetry.


Parallel optical pyramidal image processing.
Pyramidal processing is a form of multiresolution image processing in which the image is decomposed into a sequence of images at different resolutions. Pyramidal processing aims to extract and interpret significant features of an image at different resolutions. Digital pyramidal image processing, because of the large number of convolution- type operations, is time consuming. On the other hand, optical pyramidal processors, described here, are preferable in real-time image-understanding applications because of their ease in performing convolution operations. Preliminary experimental results for optical Gaussian and Laplacian pyramidal image processing are presented.


Crystal methamphetamine use and sexual risk behaviors among HIV-positive and HIV-negative men who have sex with men in South Florida.
Using data collected through venue-based sampling in South Florida from 2004 to 2005 as part of the Centers for Disease Control and Prevention-funded National HIV Behavioral Surveillance Among Men Who Have Sex with Men, we estimate the prevalence of crystal methamphetamine use and its association with high-risk sexual behaviors among a large and diverse sample of men who have sex with men (MSM) residing in South Florida. We also examine how these associations differ between HIV-positive and HIV-negative men. Bivariate analyses were used to assess the characteristics of study participants and their sexual risk behaviors by drug use and self-reported HIV status group. Of 946 MSM participants in South Florida, 18% reported crystal methamphetamine use in the past 12 months. Regardless of self-reported HIV status, crystal methamphetamine users were more likely to report high-risk sexual behaviors, an increased number of non-main sex partners, and being high on drugs and/or alcohol at last sex act with a non-main partner. Our findings indicate that crystal methamphetamine use is prevalent among the MSM population in South Florida, and this prevalence rate is similar, if not higher, than that found in US cities that have been long recognized for having a high rate of crystal methamphetamine use among their MSM populations. Notably, the use of crystal methamphetamine among both HIV-positive and HIV-negative MSM is associated with increased HIV-related risk behaviors.


The steroid vitamin D3 reduces cell proliferation in human duodenal epithelium.
1. The active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3, controls calcium absorption in the human duodenum, an effect that is mediated by mucosal vitamin D receptor expression. Functional vitamin D receptor signalling in the human colon is suggested by the reduced colonic mucosal cell proliferation seen in response to 1,25-dihydroxyvitamin D3. Thus 1,25-dihydroxyvitamin D3 might be expected to reduce cell proliferation in the small-bowel epithelium. 2. We have used an organ-culture system combined with the metaphase arrest technique to study the effects of 1,25-dihydroxyvitamin D3 on human duodenal mucosal proliferation. To validate our technique, multiple human mucosal explants were established in organ culture and vincristine (0.6 micrograms/ml) was added at 10 h. Explants were removed sequentially from 10 to 15 h and metaphase arrest figures were demonstrated by using the Feulgen reaction. The mean number of metaphase arrest figures was plotted against time in culture to show a linear accumulation of metaphases between 11 and 15 h (correlation coefficient = 0.93, r2 = 0.87, P < 0.0001). The mean crypt cell production rate was 2.01 (0.27) cells/h per crypt. 3. Paired normal duodenal mucosal biopsies from six patients were then established in organ culture with or without 10(-10) mol/l (100 pmol/l) 1,25-dihydroxyvitamin D3. The crypt cell production rate was determined between 12 and 15 h after vincristine-induced metaphase arrest. 1,25-Dihydroxyvitamin D3 reduced the median crypt cell production rate from 2.42 (1.15-4.82) to 1.41 (0.03-2.05) cells/h per crypt (P < 0.05). Thus, vitamin D3 reduces human duodenal epithelial cell proliferation.


In situ visualization of high genetic diversity in a natural microbial community.
Simultaneous in situ visualization of seven distinct bacterial genotypes, all affiliated with the phylogenetically narrow group of beta-1 Proteobacteria, was achieved in activated sludge. This finding indicates that the high diversity found in the same sample by direct rRNA sequence retrieval was indeed present in this complex community. By the combination of comparative rRNA sequence analysis, in situ hybridization with fluorescently labeled, rRNA-targeted oligonucleotides and confocal laser scanning microscopy several microbial populations can be analyzed for abundance, relative spatial distribution and phylogeny directly at their site of action without prior cultivation.